BARCELONA – First-line flat-dose nivolumab plus weight-based ipilimumab was safe and showed encouraging clinical activity both in general and in patients with poor performance status and comorbidities in the multicenter CheckMate 817 study of patients with advanced non–small cell lung cancer.
The treatment-related adverse event (TRAE) rate in 139 patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 2, for example, was 63%, compared with 77% in 391 patients with good ECOG PS (score of 0-1), and the rates of grade 3-4 AEs in the groups, respectively, were 26% and 35%, Fabrice Barlesi, MD, reported at the World Conference on Lung Cancer.
In 59 patients with ECOG PS of 0-1 plus either asymptomatic untreated brain metastases, hepatic or renal impairment, or HIV infection, the overall TRAE and grade 3-4 TRAE rates were 78% and 34%.
The combined TRAE and grade 3-4 TRAE rates in the two “special populations” cohorts were 67% and 28%, respectively, Dr. Barlesi, of Aix-Marseille Universite and Assistance Publique Hôpitaux de Marseille, France, said at the conference, which was sponsored by the International Association for the Study of Lung Cancer.
The overall response rate (ORR) in the ECOG PS-2 and PS-01+comorbidity groups was 19% and 37%, respectively, compared with 36% in the good PS cohort, and median duration of response in the three groups was 14.2 months, 9.7 months, and at least 18 months (median not reached), respectively.
The 1-year PFS rates were 25%, 27%, and 35% respectively, and median PFS was 3.6, 4.2, and 5.8, he said.
Among the 198 special population patients, those with PD-L1 expression of 50% or greater, 1% or greater, or less than 1% had 1-yr PFS rates of 46%, 24%, and 29% (median, 9.6, 3.2, and 3.9 months), and in those with 10 or greater mut/Mb and less than 10 mut/Mb, they were 42% and 17% (median, 8.3 and 2.8 months), respectively.
The single-arm, nonrandomized CheckMate 817 study evaluated the programmed death-ligand 1 (PD-L1) inhibitor nivolumab at a flat dose of 240 mg given intravenously every 2 weeks plus the CTLA-4 inhibitor ipilimumab at 1 mg/kg IV every 6 weeks, with treatment until disease progression or unacceptable toxicity for up to 2 years. Participants had stage IV non–small cell lung cancer (NSCLC), had received no prior systemic therapy, and had no known sensitizing EGFR or ALK alterations.
“Nivolumab and ipilimumab are immune checkpoint inhibitors with distinct ... but complementary mechanisms of action,” Dr. Barlesi said, adding that in combination they have demonstrated clinical benefit vs. chemotherapy in the first-line treatment of NSCLC.
However, data are limited on safety and efficacy of immunotherapy in patients with advanced NSCLC with other comorbidities such as brain metastases, kidney and renal disease, and HIV, as such patients – despite comprising the majority of NSCLC patients at presentation – are typically ineligible for trial registration, he explained, adding that CheckMate 817 is a multicohort, nonrandomized, phase 3b study evaluating the safety and efficacy of nivolumab plus ipilimumab in such patients.
The findings show a safety profile “clearly comparable” to that observed in prior studies using weight-based nivolumab, he noted.
“Nivolumab plus ipilimumab showed clearly encouraging clinical activity in this special population, with an overall response rate of 24%,” he said. “As expected, unfortunately, the outcomes in these special populations were affected by poor performance status, however, despite the poor performance status or comorbidities, those patients were shown to achieve durable responses ... with [an overall] duration of response at 1 year, of 57%.”
CheckMate 817 was sponsored by Bristol-Myers Squibb. Dr. Barlesi disclosed financial relationships with Abbvie, ACEA, Amgen, Astra-Zeneca, Bayer, Bristol-Myers Squibb, Boehringer–Ingelheim, Eisai, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Genentech, Ipsen, Ignyta, Innate Pharma, Loxo, Novartis, Medimmune, Merck, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis, and Takeda.
SOURCE: Barlesi F et al. WCLC 2019: Abstract .